INVESTIGADORES
FAINBOIM Leonardo
artículos
Título:
The tumor antigen N-Glycolyl-GM3 is a human CD1d ligand capable of mediating B cell and natural killer T cell interaction
Autor/es:
GENTILI, MV; PEREZ, M.E.; FERNANDEZ, P.; FAINBOIM, L. ; ARANA, E
Revista:
CANCER IMMUNOLOGY IMMUNOTHERAPY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2016
ISSN:
0340-7004
Resumen:
Abstract The expression of N-glycolyl-monosialodihexosyl-ganglioside (NGcGM3) in humans is restricted to cancercells; therefore, it is a tumor antigen. There are measurablequantities of circulating anti-NGcGM3 antibodies(aNGcGM3 Abs) in human serum. Interestingly, some peoplehave circulating Ag-specific immunoglobulins G (IgGs)that are capable of complement mediated cytotoxicityagainst NGcGM3 positive cells, which is relevant for tumorsurveillance. In light of the chemical nature of Ag, we postulatedit as a candidate ligand for CD1d. Furthermore, wehypothesize that the immune mechanism involved in thegeneration of these Abs entails cross talk between B lymphocytes(Bc) and invariant natural killer T cells (iNKT).Combining cellular techniques, such as flow cytometry andbiochemical assays, we demonstrated that CD1d binds toNGcGM3 and that human Bc present NGcGM3 in a CD1dcontext according to two alternative strategies. We alsoshowed that paraformaldehyde treatment of cells expressingCD1d affects the presentation. Finally, by co-culturingprimary human Bc with iNKT and measuring Ki-67expression, we detected a reproducible increment in theproliferation of the iNKT population when Ag was on themedium. Our findings identify a novel, endogenous, humanCD1d ligand, which is sufficiently competent to stimulateiNKT. We postulate that CD1d-restricted Bc presentationof NGcGM3 drives effective iNKT activation, an immunologicalmechanism that has not been previously describedfor humans, which may contribute to understandingaNGcGM3 occurrence.